The alveolar ridge at an extraction site is characterized by progressive bone loss, a common and serious clinical problem termed residual ridge resorption (RRR). The pathogenesis of RRR is not clear, but disuse (lack of functional stimulation) has been widely considered a cause. The in vivo mechanical environment of the extraction site, however, has never been characterized. While it is likely true that multiple extractions reduce masticatory stimulation to the bone, this may not be the case for a single-tooth extraction. Masticatory loading, as reflected by bone strain at a single-tooth extraction site, may be increased rather than decreased because 1) occlusal force is not necessarily reduced with a single extraction, and 2) the structural resistance of alveolar bone to occlusal force is compromised due to trauma and the loss of tooth root support. Using a pig model, we propose to measure and compare masticatory strain at the buccal alveolar bone of an extraction site and a contralateral non-extraction (control) site immediately (baseline control) and 6 weeks (experimental) after the extraction (Aim 1). These studies will provide the first direct recordings of functional mechanics surrounding a single-tooth extraction site. Further, we will investigate the post-extraction change of the alveolar bone as compared to the control side and correlated with mechanical strains (Aim 2). Alveolar bone structure and remodeling will be examined using histomorphometric methods. Cellular features including proliferation and osteoclastogenesis will be examined by immunohistochemical methods. Expression of bone remodeling (OPG, RANKL and RANK) and differentiation (Runx2) regulators will be examined using real-time RT-PCR and Western blot techniques. Overall, we hypothesize that alveolar bone at a single-extraction site will be overstrained during mastication due to its compromised structural resistance to loading, which will stimulate alveolar bone remodeling and lead to bone loss (RRR). This study features a direct characterization of the mechanical environment at a single-tooth extraction site and clarifies the relationship between functional mechanics and RRR. The findings of this study will contribute in directing the course of future research on the pathogenesis and prevention of this severe clinical entity affecting millions. Public Health Relevance: Tooth loss, a clinical entity affecting millions, leaves a residual alveolar ridge undergoing progressive bone resorption. Restoring an absorbed edentulous ridge is challenging and costly. The proposed research will characterize functional (masticatory) mechanics, a critical factor for bone metabolism, at a single-tooth extraction site alveolar ridge and examine its relationship with bone change. The results will guide researchers and clinicians in seeking effective preventive strategies for this disease.